Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural products

  • Fumitaka KudoEmail author
  • Akimasa Miyanaga
  • Tadashi Eguchi
Natural Products - Original Paper


Nonproteinogenic amino acids are the unique building blocks of nonribosomal peptides (NRPs) and hybrid nonribosomal peptide–polyketides (NRP–PKs) and contribute to their diversity of chemical structures and biological activities. In the biosynthesis of NRPs and NRP–PKs, adenylation enzymes select and activate an amino acid substrate as an aminoacyl adenylate, which reacts with the thiol of the holo form of the carrier protein to afford an aminoacyl thioester as the electrophile for the condensation reaction. Therefore, the substrate specificity of adenylation enzymes is a key determinant of the structure of NRPs and NRP–PKs. Here, we focus on nonproteinogenic amino acid selective adenylation enzymes, because understanding their unique selection mechanisms will lead to accurate functional predictions and protein engineering toward the rational biosynthesis of designed molecules containing amino acids. Based on recent progress in the structural analysis of adenylation enzymes, we discuss the nonribosomal codes of nonproteinogenic amino acid selective adenylation enzymes.


Nonproteinogenic amino acid Nonribosomal code/specificity-conferring code Structure of adenylation enzyme Engineering of adenylation enzyme Natural product biosynthesis 



This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) through a Grant-in-Aid for Scientific Research in Innovative Areas (17H05434 to F. K. and 16H06451 to T. E.), The Uehara Memorial Foundation (to F. K.) and the Japan Society for the Promotion of Science A3 Foresight Program.


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  1. 1.Department of ChemistryTokyo Institute of TechnologyTokyoJapan

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